The play is set in the small town of Mesalia, Ohio in the weeks leading to Christmas in the late 1930s. The exposition reveals that the famously outlandish New York City radio wit Sheridan Whiteside (‘Sherry’ to his friends) is invited to dine at the house of the well-to-do factory owner Ernest W. Stanley and his family. But before Whiteside can enter the house, he slips on a patch of ice outside the Stanleys’ front door and injures his hip. Confined to the Stanleys’ home, Whiteside is looked after by several professionals: Dr. Bradley, the absent-minded town physician, Miss Preen, his frantic nurse, and Maggie Cutler, his faithful secretary.

Confined to the house for a month, Sherry drives his hosts mad by viciously insulting them, monopolizing their house and staff, running up large phone bills, and receiving many bizarre guests, including paroled convicts.